We propose to expand the scope of our Human Genome Center, with the primary purpose of constructing comprehensive physical maps of the mouse and human genomes having a high degree of coverage and connectivity. We will aim to produce the majority of the physical maps within the next three years, and to use the final two years to come as close as possible to complete closure. Specifically, the Center will involve four research projects: Project 1 will produce a genetic map of the mouse consisting of 6,000 simple sequence length polymorphisms (SSLPs) and will produce a physical map of the mouse by performing STS-content mapping of the 6,000 SSLPs and 4,000 random STSs in a large-insert YAC library to assemble large contigs covering the vast majority of the genome and then approach closure in a directed fashion. Project 2 will produce a physical map of the human by performing STS- content mapping on 5,000 human SSLPs (generated by collaborators in Paris) and 5,000 random STSs in a large-insert YAC library to assemble large contigs covering the vast majority of the genome and the approach closure in a directed fashion. Project 3 will develop key technology needed to exploit the mouse and human maps to study biological function in vivo. Specifically, the project will develop efficient protocols for routine introduction of arbitrary YACs into the mouse germline. The Center will also have six core facilities -- providing support for informatics, DNA sequencing, instrumentation, construction and distribution of biological materials (such as YAC libraries), and administration.